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Mechanisms of IVIG efficacy in chronic inflammatory demyelinating polyneuropathy


Tackenberg, B; Nimmerjahn, F; Lünemann, J D (2010). Mechanisms of IVIG efficacy in chronic inflammatory demyelinating polyneuropathy. Journal of Clinical Immunology, 30(Sup 1):S65-S69.

Abstract

BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common treatable acquired chronic polyneuropathy. Corticosteroids, plasmapheresis and intravenous immunoglobulins (IVIG) have been shown to be effective in randomized controlled clinical trials and IVIG is widely used as a first-line initial and maintenance treatment for CIDP. Studies in animal models of autoimmune diseases indicated that the inhibitory Fc-gamma receptor FcgammaRIIB, expressed on myeloid cells and B cells, is required for the anti-inflammatory activity of IVIG. SUMMARY: We found that untreated patients with CIDP, compared to demographically matched healthy controls, show lower FcgammaRIIB expression levels on naïve B cells and fail to upregulate or to maintain upregulation of FcgammaRIIB as B cells progress from the naive to the memory compartment. Furthermore, FcgammaRIIB protein expression is upregulated on B cells and monocytes following clinically effective IVIG therapy suggesting that impaired expression of the inhibitory FcgammaR in CIDP can, at least partially, be restored by IVIG treatment. In B cells, FcgammaRIIB transduces an inhibitory signal upon colligation with the B cell receptor, thereby preventing B cells with low affinity or self-reactive receptors from entering the germinal center and becoming IgG positive plasma cells. Our data suggest that this late B cell differentiation checkpoint is impaired in CIDP. Modulating FcgammaRIIB function might be a promising approach to efficiently limit antibody-mediated immunopathology in CIDP.

BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common treatable acquired chronic polyneuropathy. Corticosteroids, plasmapheresis and intravenous immunoglobulins (IVIG) have been shown to be effective in randomized controlled clinical trials and IVIG is widely used as a first-line initial and maintenance treatment for CIDP. Studies in animal models of autoimmune diseases indicated that the inhibitory Fc-gamma receptor FcgammaRIIB, expressed on myeloid cells and B cells, is required for the anti-inflammatory activity of IVIG. SUMMARY: We found that untreated patients with CIDP, compared to demographically matched healthy controls, show lower FcgammaRIIB expression levels on naïve B cells and fail to upregulate or to maintain upregulation of FcgammaRIIB as B cells progress from the naive to the memory compartment. Furthermore, FcgammaRIIB protein expression is upregulated on B cells and monocytes following clinically effective IVIG therapy suggesting that impaired expression of the inhibitory FcgammaR in CIDP can, at least partially, be restored by IVIG treatment. In B cells, FcgammaRIIB transduces an inhibitory signal upon colligation with the B cell receptor, thereby preventing B cells with low affinity or self-reactive receptors from entering the germinal center and becoming IgG positive plasma cells. Our data suggest that this late B cell differentiation checkpoint is impaired in CIDP. Modulating FcgammaRIIB function might be a promising approach to efficiently limit antibody-mediated immunopathology in CIDP.

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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Psychiatry and Psychotherapy
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2010
Deposited On:16 Jan 2011 20:50
Last Modified:05 Apr 2016 14:30
Publisher:Springer
ISSN:0271-9142
Publisher DOI:10.1007/s10875-010-9398-1
PubMed ID:20424898
Permanent URL: http://doi.org/10.5167/uzh-40812

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